WO2005027967A1 - Composition medicinale - Google Patents

Composition medicinale Download PDF

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Publication number
WO2005027967A1
WO2005027967A1 PCT/JP2003/011847 JP0311847W WO2005027967A1 WO 2005027967 A1 WO2005027967 A1 WO 2005027967A1 JP 0311847 W JP0311847 W JP 0311847W WO 2005027967 A1 WO2005027967 A1 WO 2005027967A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
insulin
vitamin
insulin sensitizer
composition according
Prior art date
Application number
PCT/JP2003/011847
Other languages
English (en)
Japanese (ja)
Inventor
Kaname Kawasugi
Original Assignee
Kaname Kawasugi
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kaname Kawasugi filed Critical Kaname Kawasugi
Priority to JP2005509041A priority Critical patent/JP5140881B2/ja
Priority to US10/572,557 priority patent/US7625916B2/en
Priority to PCT/JP2003/011847 priority patent/WO2005027967A1/fr
Priority to AU2003266526A priority patent/AU2003266526A1/en
Publication of WO2005027967A1 publication Critical patent/WO2005027967A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A61K31/51—Thiamines, e.g. vitamin B1
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the present invention relates to a pharmaceutical composition, and more particularly, to a pharmaceutical composition containing an insulin sensitizer as a main drug and reducing the side effects of edema, Daishin-shinoda, and anemia caused by the drug.
  • Insulin resistance is a condition in which more than the usual amount of insulin is required to obtain the actions of insulin at the cell, organ, or individual level. This condition is a condition in which insulin sensitivity in the liver, skeletal muscle and adipose tissue is reduced, and is a characteristic condition of type 2 diabetes with insufficient insulin secretion. Insulin resistance is significantly involved not only in diabetes and impaired glucose tolerance but also in the pathogenesis of lifestyle-related diseases such as hypertension and hyperlipidemia, and its improvement has become clinically important.
  • Such inhibitors that suppress insulin resistance and can be used as insulin sensitizers include the nuclear receptor peroxisome proliferator it and the peroxisome proliferator- Activated receptor (PPAR)
  • PPAR-activation activation compound A compound having an active aconistin activity (hereinafter referred to as "PPAR-activation activation compound”) is known, and a part thereof is used for type 2 diabetes. They have an effect of improving lipid metabolism in addition to the effect of lowering blood glucose.
  • Thiazolezine compounds and non-thiazolidin compounds are known as PPAR-activation-promoting compounds.
  • thiazolidine compounds include troglitazone (trogl i tazone), piglitazone (piogl ⁇ tazon), rosiglitazone (rosigli tazone), thiazolidine-based PPAR-alpha activation promoting compounds such as CS-011, and TAK-55 9.
  • Non-thiazolidine-based PPAR- ⁇ activation promoting compounds such as FK-614 are known.
  • insulin sensitizers mainly act on adipocytes via PPAR ⁇ to promote adipocyte differentiation and suppress insulin-inducing factors such as TNF- ⁇ , resulting in insulin resistance. It is thought to improve resistance, but details are unknown.
  • Edema as a side effect has been observed in almost all thiazolidine compounds currently under development.However, if edema as a side effect is strong, it may be necessary to discontinue treatment. In some cases, diuretics are required, and this is a major problem for use as a drug.
  • an object of the present invention is to provide a technique for reducing such side effects. Disclosure of the invention
  • the present inventors have conducted intensive studies on the causes of the above-mentioned side effects of insulin sensitizers in order to solve the above-mentioned problems.By administering the insulin sensitizers, vitamins in the living body were relatively reduced. Found to be deficient. Then, they have found that the side effect can be prevented by administering vitamin B together with an insulin sensitizer, thereby completing the present invention.
  • the present invention provides a pharmaceutical composition comprising an insulin sensitizer and vitamin B or a derivative thereof.
  • examples of the insulin sensitizer used include compounds having a PPARTagonist activity. More specifically, thiazolidine PPAR-r activation promoting compounds such as pioglitazone, rosiglitazone, rosiglitazone, and CS-011, TAK-555, FK And non-thiazolidine-based PPAR- ⁇ activation promoting compounds such as -614. These can be used as a pharmaceutically acceptable derivative such as a salt thereof, if necessary.
  • Particularly preferred insulin sensitizers include thiazolidine-based PPAR-activation-promoting compounds such as pigurigurizone and mouth sigliyuzone, and derivatives such as salts thereof.
  • vitamin B used in the pharmaceutical composition of the present invention is: It is a well-known water-soluble vitamin, and has few side effects even if overdosed, and is inexpensive. Derivatives of this vitamin are also well known, and include, for example, fursultiamine, benph thiamine, succinthiamine, prosultiamine, bispentiamine, diestiamine hydrochloride, thiamine hydrochloride, thiamine disulfide, cocarboxylase and the like. Can be
  • vitamin in producing the pharmaceutical composition of the present invention, the above-mentioned insulin resistance improving agent and vitamin or a derivative thereof (hereinafter, referred to as “vitamin”) are combined with a suitable pharmaceutically acceptable carrier, and mixed.
  • a suitable pharmaceutically acceptable carrier for example, a suitable pharmaceutically acceptable carrier, and a suitable pharmaceutically acceptable carrier, and mixed.
  • the desired dosage form may be used later.
  • the compounding amount of the insulin sensitizer per 1 unit of the pharmaceutical composition of the present invention is preferably 5 to 30 mg, and the compounding amount of vitamin B and the like is 1 to 5 mg. Preferably, it is 0 O mg.
  • the mixing ratio of the insulin sensitizer and vitamin B, etc. is not particularly limited, but vitamin B, etc. is added in an amount of 0.01 to 200 parts by weight with respect to 1 part by weight of the insulin sensitizer. Parts by weight, preferably about 0.05 to 40 parts by weight.
  • the preferred formulation in the case of using pita-glitazone hydrochloride which is the only insulin-improving agent currently available in Japan, will be described below. That is, the dose (oral administration) of piglitazone hydrochloride is 15 to 45 mg once a day, and this amount should be contained in the drug per dosage unit.
  • the dose (oral administration) of piglitazone hydrochloride is 15 to 45 mg once a day, and this amount should be contained in the drug per dosage unit.
  • fursultiamine is used as vitamins B
  • 5 to 10 mg of fursultiamine may be blended per dosage unit. This amount may be the same when fursultiamine is replaced by another vitamin B, such as benfothiamine.
  • the dosage form of the pharmaceutical composition of the present invention can be a solid preparation such as a powder, a granule, a granule, a tablet, a capsule or the like, or a liquid preparation such as a liquid.
  • the carrier used in the production of the pharmaceutical composition of the present invention is not particularly limited, and a powdery or liquid carrier can be used according to the intended dosage form. Further, if necessary, appropriate additives used in the field of pharmaceuticals can be added.
  • an insulin sensitizer and vitamin B, etc. may be separately formulated and combined into a dosage form.
  • insulin enhances the renal Na reabsorption promotion effect, direct renal Na HCO 3 -co-transporter promotion effect, blood VEGF level It has been reported that vascular permeability may be increased due to an increase in the amount. Cardiac enlargement and anemia are thought to be caused by the increase in circulating plasma volume.
  • the present inventor has found that one of the causes of the above side effects is an increase in the demand for vitamins in a living body caused by the action of an insulin sensitizer.
  • the effect of the present invention is to administer vitamin B, together with an insulin sensitizer, to prevent and improve the relative deficiency of vitamins in the living body, and to reduce the side effects of edema, heart enlargement and anemia. Things.
  • Example 1 Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to these Examples.
  • Example 1
  • the relative weight ratio of the heart after administration of the benf-year-old thiamine combination group was lighter than that of the group administered with pi-year-old glitazone hydrochloride alone, and there was a tendency to improve the increase in heart weight (cardiac hypertrophy) Was done.
  • the pharmaceutical composition of the present invention using an insulin sensitizer in combination with vitamin B, etc. may cause side effects such as edema, cardiac enlargement, and anemia, even though the drug is mainly an insulin sensitizer. It does not have its efficacy and does not decrease its efficacy.
  • the vitamins used in combination have almost no side effects even if they are overdosed, and are relatively inexpensive. It is also economically excellent.
  • the pharmaceutical composition of the present invention can be used for the purpose of lowering blood glucose for type 2 diabetes.
  • the insulin sensitizer contained in the pharmaceutical composition of the present invention has a lipid metabolism improving effect, an antitumor effect, an antirheumatic effect, etc. It can also be used as an antitumor drug, antirheumatic drug, etc.

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  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne une composition médicinale qui contient un médicament améliorant la résistance à l'insuline ainsi que de la vitamine B1 ou son dérivé. Avec cette composition médicinale, on empêche les effets secondaires du médicament améliorant la résistance à l'insuline tels que l'oedème, la dilatation cardiaque, l'anémie, etc., au moyen de la vitamine B1 ou de son dérivé. Cette composition est utilisée comme traitement contre le diabète ou les maladies liées au mode de vie, comme agent antitumoral, comme médicament antirhumatoïde, etc..
PCT/JP2003/011847 2003-09-17 2003-09-17 Composition medicinale WO2005027967A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2005509041A JP5140881B2 (ja) 2003-09-17 2003-09-17 医薬組成物
US10/572,557 US7625916B2 (en) 2003-09-17 2003-09-17 Medicinal composition
PCT/JP2003/011847 WO2005027967A1 (fr) 2003-09-17 2003-09-17 Composition medicinale
AU2003266526A AU2003266526A1 (en) 2003-09-17 2003-09-17 Medicinal composition

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2003/011847 WO2005027967A1 (fr) 2003-09-17 2003-09-17 Composition medicinale

Publications (1)

Publication Number Publication Date
WO2005027967A1 true WO2005027967A1 (fr) 2005-03-31

Family

ID=34362486

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/011847 WO2005027967A1 (fr) 2003-09-17 2003-09-17 Composition medicinale

Country Status (4)

Country Link
US (1) US7625916B2 (fr)
JP (1) JP5140881B2 (fr)
AU (1) AU2003266526A1 (fr)
WO (1) WO2005027967A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3502674A (en) * 1966-11-02 1970-03-24 Shionogi Seiyaku Kk Thiol-type thiamine thionocarbonates
WO2002051441A1 (fr) * 2000-12-26 2002-07-04 Sankyo Company, Limited Compositions medicinales contenant un diuretique et un agent renforçant la resistance a l'insuline

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR240698A1 (es) * 1985-01-19 1990-09-28 Takeda Chemical Industries Ltd Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales
EP0842925A1 (fr) * 1987-09-04 1998-05-20 Beecham Group Plc Thiazolidinédiones substituées
US5977073A (en) * 1991-06-06 1999-11-02 Life Sciences' Technologies, Inc. Nutrient composition for treatment of immune disorders
DK0882718T3 (da) * 1995-12-28 2005-12-12 Astellas Pharma Inc Benzimidazolderivater
IL139470A0 (en) * 1998-05-11 2001-11-25 Takeda Chemical Industries Ltd Oxyiminoalkanoic acid derivatives
US6660293B2 (en) * 2001-06-29 2003-12-09 Everett Laboratories, Inc. Compositions and methods for prophylactic and therapeutic supplementation of nutrition in subjects
FR2832064A1 (fr) * 2001-11-13 2003-05-16 Lipha Composition pharmaceutique comprenant une glitazone et un derive de thiazolidinedione et son utilisation pour traiter le diabete

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3502674A (en) * 1966-11-02 1970-03-24 Shionogi Seiyaku Kk Thiol-type thiamine thionocarbonates
WO2002051441A1 (fr) * 2000-12-26 2002-07-04 Sankyo Company, Limited Compositions medicinales contenant un diuretique et un agent renforçant la resistance a l'insuline

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HASHIZUME N. ET AL.: "Vitamin B1 ketsubosho", IGAKU NO AYUMI, vol. 198, no. 13, 2001, pages 949 - 952, XP002986222 *
TAMAI H. ET AL.: "Tonyobyo to vitamin", JAPANESE JOURNAL OF CLINICAL MEDICINE, vol. 57, no. 10, 1999, pages 200 - 203, XP002986221 *

Also Published As

Publication number Publication date
AU2003266526A1 (en) 2005-04-11
US20070105910A1 (en) 2007-05-10
US7625916B2 (en) 2009-12-01
JP5140881B2 (ja) 2013-02-13
JPWO2005027967A1 (ja) 2006-11-30

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